PULMONARY ALVEOLAR MICROLITHIASIS IN AN IMMUNODEFICIENT PATIENT

Abstract

INTRODUCTION: Pulmonary alveolar microlithiasis (PAM) is a rare disease of unclear etiology characterized by diffuse formation of microscopic calculi or microliths within the alveoli. We present a unique case report of a patient with a rare type of immunodeficiency who developed alveolar microlithiasis. CASE PRESENTATION: A two year old male was referred to our clinic for assessment of chronic lung disease. He presented with chronic cough and intermittent tachypnea with minimal response to inhaled steroids and beta agonists. He had an undefined immunodeficiency consisting of low B cells, low natural killer cells and agammaglobulinemia requiring weekly immunoglobulin infusions. Previous respiratory illnesses included prolonged intensive care admission with Adult Respiratory Distress Syndrome, as well as treatment for presumed pneumocystis jiroveci. Noninvasive home ventilation had been required for respiratory insufficiency in the past. Chest radiograph revealed a diffuse pattern of interstitial lung disease. Imaging by CT scan demonstrated ground glass opacities with mild bronchial wall thickening. On subsequent transbronchial biopsy, areas of intraalveolar calcification were noted with minimal fibrotic thickening of septae. An open lung biopsy was performed which revealed bulky mineralization scattered throughout a fibrotic, chronically inflamed parenchyma. Areas of calcification were again localized to the alveoli. Serum levels of calcium, phosphate and parathyroid hormone were within normal limits.His course was further complicated by development of pancytopenia which led to a diagnosis of monosomy 7 and myelodysplastic syndrome. It was decided to proceed to bone marrow transplant due to rising peripheral blast percentage and further pneumocysitis jiroveci infection. CT chest post transplant demonstrated more confluent groundglass opacities with calcified centrilobular nodules and scattered bronchiectasis. Pulmonary symptoms remained stable. DISCUSSIONS: The etiology of PAM is unknown but familial occurrence is documented in many cases with an autosomal recessive pattern of inheritance. PAM has been noted in patients with other disorders such as azoospermia, lymphocytic interstitial pneumonitis, mitral stenosis and milk alkali syndrome. There have been no previously documented cases of patients with PAM and either immunodeficiencies or hematological disorders requiring bone marrow transplant. The impact of bone marrow transplant on PAM is unknown, however in this case to date pulmonary symptoms remain stable although radiological findings show progression of pulmonary disease.Many patients with PAM are asymptomatic and the presence of respiratory symptoms depends on the extent of pulmonaryalveolar calcification. When the disease is extensive respiratoryfailure can lead to cor pulmonale and lung transplantation with variable results.The diagnosis of PAM can be suspected on chest radiograph if the typical "sandstorm" appearance is noted. This was not present in our case and further evaluation by CT chest was used to demonstrate significant ground glass opacities. Most pediatric cases of PAM are confirmed on transbronchial biopsy where, as in this case, lung parenchyma demonstrates microliths in the alveolar spaces with associated thickened fibrotic interstitium. Pathogenesis of PAM appears to be related to deposition of calcium phosphate salts in the alveoli either by extrusion from pulmonary capillaries or other unknown mechanisms.No specific therapy has been reported for PAM and lung transplantation has been the only option for those with progressive disease. Varied results have been found with use of glucocorticoids, calcium and phosphate binders and surfactant use. No specific therapy has been advocated in our patient to date, however the use of immunosuppressant therapy may be playing an unclear role in symptom prevention.